PD is a progressive illness that is symptomatically characterised by slowness of movement (bradykinesia), rigidity and/or tremor and postural instability. Patients with PD have a deficiency of the neurotransmitter dopamine, due to chronic and progressive degeneration of the substantia nigra in the brain.
The cause of PD is unknown, however the deficiency in dopamine has led to the widespread use of dopamine-replacing agents as symptomatic treatments for the disease. The most commonly prescribed drug for this treatment is L-3,4-dihydroxyphenylalanine (L-dopa) and dopamine agonists.
These symptomatic treatments are successful in increasing the quality of life of patients suffering from PD. Such dopamine-replacement treatments do however have significant limitations, particularly in long-term treatment. These limitations include fluctuations in the efficacy of the treatment, leading to the “on-off” phenomenon and appearance of side-effects which manifest as abnormal involuntary movements.
Other than L-dopa, the most common medicaments for alleviating these motor symptoms are dopamine agonists such asrotigotine, pramipexole, bromocriptine, ropinirole, cabergoline, pergolide, apomorphine and lisuride, anticholinergic agents, N-methyl d-aspartate (NMDA) antagonists, beta-blockers as well as the Monoamine oxidase B (MAO-B) inhibitor selegeline and the Catechol-O-methyl transferase (COMT) inhibitor entacapone.
The majority of these medicaments intervene in the dopaminergic and/or cholinergic signal cascade and symptomatically influence motor disturbances.
Whilst the above symptomatic treatments can enhance the life of a PD patient, often restoring function to nearly normal for some period of time, each have side effects and no treatment provides a cure for the disease. Over time, as the disease progresses, drug dosing must be adjusted to best meet a patient's symptomatic needs.